The experiments described in this proposal extend our previous work on the interactions of alcohol (E) with the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitarygonadal (HPG) axis in the rat. In agreement with other investigators, we observed that El stimulates the HPA and inhibits the HPG axis. The present proposal will test hypotheses related to the mechanisms responsible for the endocrine consequences of E administration. Our four main goals are to: (a) define the importance of gender and age of the animals in modulating the, response of the HPA axis to E; (b) identify (using immunocytochemical and in situ hybridization techniques for the detection of c-fos/c-jun and CRF proteins) the brain pathways activated by E, and investigate their role in modulating the stimulatory effect of E on the HPA axis; (c) determine the effect of pre- and perinatal exposure to E on the HPA axis of the offspring, the neuronal pathways which are vulnerable to this treatment, as well as the ability of neonatal handling to reverse the augmented HPA axis' response caused by prenatal E; and (d) investigate the role of various brain pathways (particularly those which are CRF-dependent) in mediating the ability of E to inhibit the activity of the HPG axis. Our laboratory has extensive experience and expertise in the field of neuroendocrinology and has a multi-disciplinary approach which lends itself well to the testing of the hypotheses proposed here. We have many tools at our disposal, including a variety of animal models, surgical techniques, RIAs and molecular probes which will allow us to pursue the Aims described in this application.